Wang Minyan, Zhao Yunfei, Zhao Yue, Shi Zhuangzhi
State Key Laboratory of Coordination Chemistry, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, China.
Sci Adv. 2020 May 8;6(19):eaba0946. doi: 10.1126/sciadv.aba0946. eCollection 2020 May.
Methods to incorporate deuterium atoms into organic molecules are valuable for the pharmaceutical industry. The introduction of deuterium atoms by a synthetic method enables the direct tracing of the drug molecule without substantially altering its structure or function. The methyl group is one of the most commonly occurring carbon fragments in biologically active molecules. Here, a biomimetic design reagent, 5-(methyl- )-5-dibenzo[]thiophen-5-ium trifluoromethane sulfonate (DMTT), as an analog of -adenosylmethionine (SAM), has been developed for the selective -methylation of complex molecules bearing several possible reactive sites with excellent selectivity and high-level deuterium incorporation. A series of -methylated organic molecules and deuterated pharmaceuticals were synthesized under the mild system with excellent functional group compatibility.
将氘原子引入有机分子的方法对制药行业很有价值。通过合成方法引入氘原子能够直接追踪药物分子，而基本不改变其结构或功能。甲基是生物活性分子中最常见的碳片段之一。在此，已开发出一种仿生设计试剂5-(甲基-)-5-二苯并[]噻吩-5-鎓三氟甲磺酸酯（DMTT），作为S-腺苷甲硫氨酸（SAM）的类似物，用于对具有多个可能反应位点的复杂分子进行选择性S-甲基化，具有出色的选择性和高水平的氘掺入。在温和体系下合成了一系列S-甲基化有机分子和氘代药物，具有出色的官能团兼容性。
